This invention is directed to pharmaceutical compositions containing dyclonine hydrochloride (HCl) and phenol.
Dyclonine HCl, chemically denoted as 3-piperidino-4'-butoxypropiophenone hydrochloride, is a well known anesthetic/analgesic agent for topical use on the mucous membranes of the mouth and throat (see Federal Register, Vol. 47, No. 101, Proposed Rules, pages 22810-13, 1982). Oral pharmaceutical compositions of dyclonine HCl commercially available in the United States include an aqeuous liquid spray containing 0.1% dyclonine HCl and solid lozenges containing 1.2 mg dyclonine HCl per lozenge for children and 3.0 mg per lozenge for adults (see Physicians' Desk Reference for Nonprescription Drugs, 8th Ed., 1987, pages 518-9). The benefit of dyclonine HCl is that it provides long acting topical anesthetic relief. The use of certain acids, particularly citric acid, to stabilize dyclonine HCl in anesthetic lozenges is reported in U.S. Pat. No. 4,139,627.
In addition to its anesthetic/analgesic properties, dyclonine HCl is known to possess antimicrobial activity. In this regard, U.S. Pat. No. 2,868,689 discloses stabilized aqueous preparations of dyclonine HCl (0.1-5%) having topical anesthetic and antimicrobial action, the stabilization aspect being provided by the addition of chlorobutanol (0.1-0.5%).
It is noted, for purposes of the subject invention, that phenol was specifically identified in said U.S. Pat. No. 2,868,689 as being an unsatisfactory stabilizer (column 1, lines 60-61).
Phenol is a known topical anesthetic, which has been used to treat minor sore mouth and sore throat pain. The mode of action, fast acting but not long lasting, is that it desensitizes sensory nerve receptors present in the mucous membranes of the throat and oral cavity to exert its local anesthetic effect. Previous dosage forms of administration have included lozenges containing 32.5 mg phenol per lozenge and aqueous solutions of 1.4% phenol for use as a mouthwash, rinse or gargle, which is expelled from the oral cavity after use, and as a throat spray (see Physicians' Desk Reference for Nonprescription Drugs, 8th Ed., 1987 pages 654-5). In addition to its anesthetic activity, phenol is known to possess antimicrobial activity.
It has now been found that the combined action of dyclonine HCl and phenol in pharmaceutical compositions containing an effective topical anesthetic and antimicrobial amount of each active results in producing an enhanced antimicrobial effect beyond that which might be expected from the mere additive effect of the two actives. Without being bound to such explanation, it would seem, in view of the antimicrobial activity of each active, that said antimicrobial enhancement results from co-potentiation between the two, that is, by each active potentiating the anti-microbial activity of the other.